Self-renewal of murine embryonic stem cells is supported by the serine/threonine kinases Pim-1 and Pim-3.

I Aksoy, C Sakabedoyan, PY Bourillot, AB Malashicheva, J Mancip, K Knoblauch, M Afanassieff, P. Savatier

Research output

55 Citations (Scopus)

Abstract

pim-1 and pim-3 encode serine/threonine kinases involved in the regulation of cell proliferation and apoptosis in response to cytokine stimulation. We analyzed the regulation of pim-1 and pim-3 by the leukemia inhibitory factor (LIF)/gp130/signal transducer and activator of transcription-3 (STAT3) pathway and the role of Pim-1 and Pim-3 kinases in mouse embryonic stem (ES) cell self-renewal. Making use of ES cells expressing a granulocyte colony-stimulating factor:gp130 chimeric receptor and a hormone-dependent signal transducer and activator of transcription-3 estrogen receptor (STAT3-ER(T2)), we showed that expression of pim-1 and pim-3 was upregulated by LIF/gp130-dependent signaling and the STAT3 transcription factor. ES cells overexpressing pim-1 and pim-3 had a greater capacity to self-renew and displayed a greater resistance to LIF starvation based on a clonal assay. In contrast, knockdown of pim-1 and pim-3 increased the rate of spontaneous differentiation in a self-renewal assay. Knockdown of pim-1 a
Original languageEnglish
Pages (from-to)2996-3004
JournalStem Cells
Volume25
Issue number12
Publication statusPublished - 2007
Externally publishedYes

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